It is well known that UV light, pollution, cigarette smoke and stress can be very detrimental to skin. The skin on the face is made up of keratinocytes. Exposure to such environmental aggressors causes damage to cellular DNA. For example, it is estimated that a single sun burn results in hundreds of thousands of DNA mutagenic base modifications such as T-T (thiamine-thiamine) dimmers; 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-DG); 06MeG (06-methyl guanine); and 6-4PP (6-4 photoproducts) in affected cells. Fortunately, healthy keratinocytes have a natural internal mechanism for repairing these lesions. However, repair of DNA lesions takes time. For example, repair of TT dimers and 6-4PP damage formed by UVB exposure may take up to 48 and 8 hours respectively. Repair of 8-oxo-dG and 06MeG lesions due to UVA or UVB exposure, ozone, or smoke and pollution may take up to 2 hours. If DNA lesions are not repaired before cell division, the result is apoptosis, or cell death.
The body's natural circadian rhythms are synchronized such that during exposure to environmental aggressors—usually during daylight hours—certain genes in the cells are activated to produce proteins that protect the cells against damage. Then, during periods of rest, usually at night, gene activation is decreased with normal circadian rhythms.
Recently, genes associated with natural bodily circadian rhythms have been identified and include the CLOCK (Circadian Locomotor Output Cycles Kaput) gene and the PER1 (Period Homolog 1) gene, both of which encode proteins that regulate circadian rhythms. CLOCK and PER1 genes are also present in keratinocytes, and they promote synthesis of corresponding proteins which promote cellular viability and repair. However, with normal circadian rhythms, the genes are most activated during daylight hours. As the corresponding protein levels increase during the day, a feedback inhibition results and the genes are “turned off” as night time approaches.
Cosmetic products for application to skin prior to nightly rest are well known. Many of such products contain ingredients that help to promote the cellular repair process. For example, they may include DNA repair enzymes for improving the effectiveness of natural cellular DNA repair, humectant ingredients for maintaining keratinocyte hydration, moisturizing ingredients for improving skin barrier function, and so on. While these ingredients improve the ability of keratinocytes to repair during periods of nightly rest, there is always room for improvement.
It has been discovered that activation of CLOCK and PER1 genes present in keratinocytes results in synthesis of proteins that promote cellular viability, cellular longevity, inhibition of cellular damage due to environmental aggressors, and improved repair of DNA damage. Proteins produced by activation of CLOCK and PER1 genes are most often generated during the normal circadian rhythm cycle, that is during daylight, when the skin is most subjected to environmental aggressors.
It is an object of the invention to provide a method of inhibiting damage to human keratinocytes due to environmental aggressors by applying a composition comprising at least one keratinocyte CLOCK or PER1 gene activator and least one DNA repair enzyme.
It is a further object of the invention to provide a method for repairing skin comprising applying to the skin a composition comprising at least one keratinocyte CLOCK or PER1 gene activator either alone or in combination with at least one DNA repair enzyme.
It is a further object of the invention to provide a composition for treating skin comprising at least one keratinocyte CLOCK or PER1 gene activator either alone or in combination with at least one DNA repair enzyme.